Adagene, Inc. · NASDAQ:ADAG
Adagene — Investor Presentation (July 2023)
31 slides from Adagene's investor presentation, Jul 7, 2023
Slide 1: Unleashing Anti-CTLA-4 Therapy By Enhancing the Therapeutic Index
Unleashing Anti - CTLA - 4 Therapy By Enhancing the Therapeutic Index July 2023
Slide 2: Disclaimer and Cautionary Note on Forward-Looking Statements
Disclaimer and Cautionary Note on Forward - Looking Statements The following presentation has been prepared by Adagene Inc . (“Adagene” or the “Company”) solely for informational purposes and should not be construed to be, directly or indirectly, in whole or in part, an offer to buy or sell and/or a
Slide 3: Why Focus on Next Generation Anti-CTLA-4 Therapies?
Why Focus on Next Generation Anti - CTLA - 4 Therapies? - CTLA - 4 is a proven target with a need to “troubleshoot” safety to maximize its therapeutic potential • Only approved checkpoint inhibitor for both single agent & combination use besides anti - PD - (L)1 therapies - Treg depletion is crucial
Slide 4: A New Paradigm for Anti-CTLA-4 Therapy: Targeting CTLA-4 in the Tumor Microenvironment
A New Paradigm for Anti - CTLA - 4 Therapy: Targeting CTLA - 4 in the Tumor Microenvironment 4 Thesis for first generation anti - CTLA - 4 therapies: Efficacy is driven by T cell activation through CTLA - 4 blockade. By widening the therapeutic window, Adagene is taking anti - CTLA - 4 therapy to th
Slide 5: Adagene Product Candidates are Focused on Unleashing the Potential of Anti-CTLA-4 Therapy
Adagene Product Candidates are Focused on Unleashing the Potential of Anti - CTLA - 4 Therapy by Enhancing the Therapeutic Index (TI) - Two unique anti - CTLA - 4 candidates in phase 1b/2 studies: • ADG116 NEObody Я targets a unique binding site • ADG126 SAFEbody ® is masked version of ADG116 • Dose
Slide 6: Dynamic Precision Library & Antibody Technologies Enable Wider Therapeutic Window
Dynamic Precision Library & Antibody Technologies Enable Wider Therapeutic Window for Anti - CTLA - 4 & Other Immunotherapies POWERbody 瀧 NEObody 瀧 SAFEbody ® 6 Masking peptide Enhanced Fc ▪ Precision masking for antibody safety ▪ Further expands TI by preferential targeting of CTLA - 4, which is hi
Slide 7: The Challenge: Uncouple Dose-dependent Efficacy from Toxicity of Anti-CTLA-4
The Challenge: Uncouple Dose - dependent Efficacy from Toxicity of Anti - CTLA - 4 as Monotherapy and in Combination with Anti - PD - 1 Agents 7 Anti - CTLA - 4 Ipilimumab Dosage (mg/kg) m - OS (years) ≥ Gr 3 TRAEs, % Discontinuation Rate, % Monotherapy 1L Melanoma 10 1.3 36% 34% 3 1 20% 19% Combine
Slide 8: Improving Safety of Anti-CTLA-4 Therapies Will Enable Improved Tolerability
Improving Safety of Anti - CTLA - 4 Therapies Will Enable Improved Tolerability of Higher Effective Doses and Longer Administration 8 Safety is ‘The Holy Grail’* for Anti - CTLA - 4 Therapy to Unleash Efficacy *Report by D. Graybosch, SVB Leerink, Nov 2022 ▪ Safety as monotherapy at higher effective
Slide 9: Our Next Generation Anti-CTLA-4 Therapies Expand the Therapeutic Index
Our Next Generation Anti - CTLA - 4 Therapies Expand the Therapeutic Index 9 Dosage AUC ss , tumor ISF fold difference C max,ss,tumor ISF fold difference Masked ADG126 (10 mg/kg Q3W) vs. Ipilimumab (1 mg/kg Q6W) ~ 27 x ~ 9 x Unmasked ADG116 (3 mg/kg Q3W) vs. Ipilimumab (1 mg/kg Q6W) ~4 x ~3 x • ADG1
Slide 10: ADG116: Our NEObody Solution
ADG116: Our NEObody Solution 10
Slide 11: ADG116: Single Agent and Combination Efficacy with Repeat Dosing and Enhanced TI
ADG116: Single Agent and PD - 1 Combination Efficacy with Repeat Dosing and Enhanced TI 11 ORR is reported in e valuable patients with at least one valid post - baseline tumor assessment. ADG116 data from ADG116 - 1003 and ADG116 - 1002 studies as of May 2023. - Favorable safety profile for ADG116 m
Slide 12: Design for ADG116 + Anti-PD-1 Combination Evaluation
Design for ADG116 + PD - 1 Combination Evaluation 12 Dose Optimization with Anti - PD - 1 • Prior monotherapy dose escalation conducted up to 15 mg/kg Q3W • Prior combination dose escalation* conducted with either pembrolizumab (200 mg Q3W) or toripalimab (240 mg Q3W) • Dose optimization/expansion o
Slide 13: ADG116 Monotherapy: Repeat Dosing Demonstrates Continuing Clinical Benefit
ADG116 Monotherapy: Repeat Dosing (>7 cycles) Enabled by Safety Profile Demonstrates Continuing Clinical Benefit 13 Baseline 6 weeks 12 weeks 21 weeks Target Lesion TL 1 - Lymph Node 19 mm 17 mm 10 mm 10 mm TL 2 - Lymph Node 31 mm 27 mm 19 mm 15 mm Sum 50 mm 44 mm ( - 12%) 29 mm ( - 42%) 25 mm ( - 5
Slide 14: ADG116 Monotherapy: Additional PR in IO-experienced RCC Patient
ADG116 Monotherapy: Additional PR Further Reinforces Safety & Efficacy Profiles with Repeat Dosing in IO - experienced RCC Patient Confidential 14 Subject: Male, 56 years old Tumor Type: Clear cell renal cell carcinoma Site Location: South Korea Dose Regimen : 10 mg/kg ADG116 (13 cycles @ Q3W) Prior
Slide 15: ADG116 + Combination: Rapid Complete Response in HNSCC Patient
Baseline Week 6 Week 18 Week 50 Target Lesion TL1 - Right mandibular 32 mm Disappeared Disappeared Disappeared TL2 - Right submandibular 18 mm Disappeared Disappeared Disappeared TL3 - Lymph node 15 mm 8 mm 5 mm 5 mm Sum 65 mm 8 mm 5 mm 5 mm Non - target Lesions 3 Present Disappeared Disappeared Dis
Slide 16: ADG116 + Combination: Initial Partial Response in MSS CRC
ADG116 + PD - 1 Combination with Repeat Dosing: Initial Partial Response in MSS CRC Observed Within Two Cycles 16 Baseline 6 weeks Target Lesion TL1 - LN (right paraaortic) 25 mm 15 mm TL2 - LN (common iliac) 20 mm 15 mm Sum (percent change) 45 mm 30 mm ( - 33%) Non - Target Lesions NTL1 - LN (right
Slide 17: ADG126: Our SAFEbody Solution
ADG126: Our SAFEbody Solution 17
Slide 18: ADG126: Encouraging Efficacy Profile Observed at High Dose Levels
ADG126: Encouraging Efficacy Profile Observed with Anti - PD - 1 at High Dose Levels with Repeat Dosing and Further Enhanced TI 18 - No DLT or ≥ G3 TRAEs observed for ADG126 monotherapy up to 20 mg/kg Q3W (N=30) - Safety profile of ADG126 + PD - 1 dose escalation demonstrates best - in - class poten
Slide 19: Design for ADG126 + Anti-PD-1 Combination Evaluation
Design for ADG126 + Anti - PD - 1 Combination Evaluation 19 Dose Escalation with Anti - PD - 1 • Prior monotherapy dose escalation conducted up to 20 mg/kg Q3W • Prior combination dose escalation* with either pembrolizumab (200 mg Q3W) or toripalimab (240 mg Q3W) • Dose expansion ongoing, primarily
Slide 20: Uncoupling Efficacy from Safety: ADG126 + Combination Unleashes Efficacy
* Early data cut from patients dosed by ADG126 + anti - PD - 1 therapies in ADG126 - 1001 study (data cutoff: Mar 14, 2023) and ADG126 - P001 study (data cutoff: Mar 9, 2023) as reported in poster presentations at AACR 2023. 20 ADG126 Dosing Regimen Patients Dosed (N) Safety Efficacy 6 mg/kg Q3W 11
Slide 21: ADG126 at 10 mg/kg Q3W Enables Repeat Dosing with Anti-PD-1
Confidential 21 - 4 PRs (4/29) have been observed in the dose escalations of ADG126 in combination with anti - PD - 1 therapy • ORR of 40% (4/10) in the ADG126 10 mg/kg Q3W cohort • One PR each for anal SCC, penile SCC, endometrial (MSI - H) and cervical cancer • 3 IO - naïve patients and one patien
Slide 22: ADG126 + Combination: Confirmed PR in a Resistant Patient
ADG126 + PD - 1 Combination: Confirmed PR with Continuous Tumor Shrinkage in a PD - 1 Resistant Patient with Low PD - L1 Expression Lesion # Location Baseline 6 Weeks 12 Weeks 18 Weeks 24 Weeks 30 Weeks Target lesion TL#1 Lymph node (Subcarinal) 25 mm 25 mm 21mm 17 mm 13 mm 9 mm TL#2 Lymph node (Pre
Slide 23: ADG126 + Combination: MSS CRC Patient Tumor Assessment
Tumor Type: Male, 53 years old, ECOG PS 0, MSS rectosigmoid adenocarcinoma with liver metastasis at baseline Site Location: Singapore Prior Therapies: Previously received curative & palliative surgery for liver metastasis and 3 lines of therapies (Leucovorin + 5FU + irinotecan + oxaliplatin; bevaciz
Slide 24: The Case for ADG126 in MSS CRC
The Case for ADG126 in MSS CRC: Evidence of Activity in Cold & Difficult - to - Treat Tumors - Objective responses and/or tumor shrinkage, and prolonged stable disease by ADG116 (unmasked parental antibody) and ADG126 in MSS CRC patients - Correlation of clinical activities with the reduction in car
Slide 25: A Path Forward for ADG126 in MSS CRC
A Path Forward for ADG126 in MSS CRC 25 - ADG126 SAFEbody is the most advanced clinical stage anti - CTLA - 4 candidate + that integrates masking technology and Treg depletion for superior safety & efficacy profiles - Dose expansion cohort of ADG126 plus pembrolizumab enrolling ~20 MSS CRC patients,
Slide 26: Next Steps & Takeaways
Next Steps & Takeaways 26
Slide 27: Status & Next Steps
Status & Next Steps Status Next Steps ADG116 • Confirming dosing regimens for future trials • Advance into Ph 2 tumor - specific cohorts ADG126 • Ongoing dose expansion at 10 mg/kg Q3W & Q6W • Randomized trial with novel triple combination in HCC • Ph 2 MSS CRC and HCC efficacy readouts 27 Establish
Slide 28: Key Takeaways
Adagene’s next - generation CTLA - 4 candidates are designed to widen the therapeutic window by targeting a unique epitope of CTLA - 4 and then combining it with precision masking technology: • Enhanced Treg depletion in TME • Repeat dosing for sustained target engagement ADG116 & ADG126 demonstrate
Slide 29: Additional Information
WN IK Additional Information
Slide 30: Both Masked and Unmasked Anti-CTLA-4 Candidates Show Favorable Safety Profiles
Both Masked and Unmasked Anti - CTLA - 4 Candidates Show Favorable Safety Profiles Compared to Historical Controls 30 ADG116 ≤ 6 mg/kg Q3W (n=30) 0% 30 10 & 15 mg/kg Q3W (n=29) 14% Ipilimumab+ 3 mg/kg Q3W 20 - 27% 10# 10 mg/kg Q3W 36% This slide contains information from various clinical trials whic
Slide 31: Reference List for Slide 7
Reference List for Slide 7 31 - Ascierto PA, et al. J Immunother Cancer 2020;8:e000391. doi:10.1136/jitc - 2019 - 000391; N ivo + 4 doses of Ipi - Larkin J, Chiarion - Sileni V, Gonzalez R, et al: Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373:23 - 34, 2015